Increased late sodium current in left atrial myocytes of rabbits with left ventricular hypertrophy: its role in the genesis of atrial arrhythmias

Guo D, Young L, Wu Y, Belardinelli L, Kowey PR, Yan G. Increased late sodium current in left atrial myocytes of rabbits with left ventricular hypertrophy: its role in the genesis of atrial arrhythmias. Am J Physiol Heart Circ Physiol 298: H1375-H1381, 2010. First published February 26, 2010; doi:10.1152/ajpheart.01145.2009.-Left ventricular hypertrophy (LVH) is frequently associated with clinical atrial arrhythmias, but little is known about how it causes those arrhythmias. Our previous studies have shown that LVH increases the late sodium current (I(Na-L)) that plays an important role in the genesis of ventricular arrhythmias. We hypothesize that LVH may also induce an upregulation of the I(Na-L) in atrial myocytes, leading to atrial electrical abnormalities. The renovascular hypertension model was used to induce LVH in rabbits. Action potential and membrane current recordings were performed in single myocytes. At a pacing cycle length of 2,000 ms, spontaneous phase-2 early afterdepolarizations (EADs) could be recorded from the left atrial myocytes in 10 of 12 LVH rabbits, whereas no EADs could be elicited in right atrial myocytes of LVH rabbits or atrial myocytes from any of the 12 control rabbits. Spontaneous automaticity (SA) from left atrial myocytes was observed in 9 out of 12 LVH rabbits, but none in right atrial myocytes of LVH rabbits or control rabbits, at a pacing rate of 8,000 ms. The left atrial myocytes of LVH rabbits had a significantly higher density of the I(Na-L) compared with those of control rabbits (0.90 +/- 0.12 in LVH vs. 0.50 +/- 0.08 pA/pF in control, n = 8, P < 0.01). Tetrodotoxin, an I(Na-L) blocker, abolished all atrial EADs and SA at 10 mu M. Our results demonstrate that LVH induction results in a significant increase of I(Na-L) in the left atrial myocytes that may render these cells susceptible to the genesis of EADs and SA. The I(Na-L) may serve as a potentially useful ionic target for antiarrhythmic drugs for the treatment of atrial arrhythmias in the setting of LVH.